Sustained B cell depletion by CD19-targeted CAR T cells is a highly effective treatment for murine lupus

• Published in: Science translational medicine Vol. 11; no. 482
• Main Authors: Kansal, Rita, Richardson, Noah, Neeli, Indira, Khawaja, Saleem, Chamberlain, Damian, Ghani, Marium, Ghani, Qurat-Ul-Ain, Balazs, Louisa, Beranova-Giorgianni, Sarka, Giorgianni, Francesco, Kochenderfer, James N, Marion, Tony, Albritton, Lorraine M, Radic, Marko
• Format: Journal Article
• Language: English
• Published: United States 06-03-2019
• Subjects: Animals; Antigens, CD19 - metabolism; B-Lymphocytes - immunology; Female; Immunotherapy, Adoptive; Lupus Erythematosus, Systemic - blood; Lupus Erythematosus, Systemic - immunology; Lupus Erythematosus, Systemic - therapy; Lymphocyte Depletion; Mice; Phenotype; Proteome - metabolism; Survival Analysis; T-Lymphocytes - metabolism
• ISSN: 1946-6242
• DOI: 10.1126/scitranslmed.aav1648

The failure of anti-CD20 antibody (Rituximab) as therapy for lupus may be attributed to the transient and incomplete B cell depletion achieved in clinical trials. Here, using an alternative approach, we report that complete and sustained CD19
B cell depletion is a highly effective therapy in lupus models. CD8
T cells expressing CD19-targeted chimeric antigen receptors (CARs) persistently depleted CD19
B cells, eliminated autoantibody production, reversed disease manifestations in target organs, and extended life spans well beyond normal in the (NZB × NZW) F
and MRL
mouse models of lupus. CAR T cells were active for 1 year in vivo and were enriched in the CD44
CD62L
T cell subset. Adoptively transferred splenic T cells from CAR T cell-treated mice depleted CD19
B cells and reduced disease in naive autoimmune mice, indicating that disease control was cell-mediated. Sustained B cell depletion with CD19-targeted CAR T cell immunotherapy is a stable and effective strategy to treat murine lupus, and its effectiveness should be explored in clinical trials for lupus.